Reaktion #450895

Reaktionsgleichung

diethyl azodicarboxylate

2,6-diaminopurine

diethyl 2-hydroxyethoxymethane-phosphonate

diethyl 2-hydroxyethoxymethanephosphonate

triphenylphosphine

DMF

→

desired N9 - product 1c

Ausbeute 23.0%

2,6-Diamino-9-(2-diethoxyphosphonomethoxyethyl)purine

Ausbeute 23.0%

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was then cooled to -30° C.
2. 2
   Temperaturwas maintained below -25° C
3. 3
   workup.STIRRINGThe reaction mixture was stirred at that temperature for 2 h
4. 4
   Temperaturto warm to ambient temperature gradually
5. 5
   workup.STIRRINGstirred overnight
6. 6
   SonstigeAny unreacted 2,6-diaminopurine was removed by filtration
7. 7
   Sonstigethe solvent removed under vacuum
8. 8
   SonstigeThe crude product was purified by silica gel column chromatography
9. 9
   Wascheneluting with CH2Cl2 /MeOH (9:1)

Vorschrift

A mixture of 2,6-diaminopurine (350 mg, 2.36 mmol), diethyl 2-hydroxyethoxymethane-phosphonate 2b (500 mg, 2.36 mmol) and triphenylphosphine (930 mg, 3.54 mmol) in anhydrous DMF (10 mL) was stirred at ambient temperature under N2 for 30 min. The reaction mixture was then cooled to -30° C. and diethyl azodicarboxylate (0.56 mL, 3.54 mmol) was added dropwise at such a rate that the reaction temperature was maintained below -25° C. The reaction mixture was stirred at that temperature for 2 h and then allowed to warm to ambient temperature gradually and stirred overnight. Any unreacted 2,6-diaminopurine was removed by filtration and the solvent removed under vacuum. The crude product was purified by silica gel column chromatography, eluting with CH2Cl2 /MeOH (9:1), to afford 190 mg (23 % yield) of the desired N9 - product 1c. An analytical sample was obtained from recrystallization using EtOAc/MeOH (5:1). mp. 152°-154° C. 1H NMR (CDCl3) δ 7.66 (s, 1 H, H-8), 6.67 (s, 2 H, NH2), 5.79 (s, 2 H, NH2), 4.13 (t, J=5.0 Hz, 2 H, CH2N), 3.95 (apparent quintet, J=7.3 Hz, 4 H, 2 OCH2CH3), 3.84 (d, J=8.4 Hz, 2 H, CH2P), 3.81 (t, J=5.0 Hz, 2 H, CH2O), 1.17 (t, J=7.1 Hz, 6 H, 2 CH3); 13C NMR (CDCl3) d 160.01, 156.08, 151.87, 138.79, 114.03 (purine ring carbons), 71.36 (d, 2JC,P= 10.8 Hz, OCH2CH3), 65.26 (d, 1JC,P=166.5 Hz, CH2P), 62.50 (d, 3JC,P=6.5 Hz, CH2O), 42.92 (CH2N), 16.44 (d, 3JC,P=5.7 Hz, CH3); UV (MeOH) λmax 255 (10,300), 281(12,000) nm; IR (KBr, cm-1) 3345 and 3177 (s, broad, NH2), 1669, 1636 and 1599 (s, purine ring), 1242 (s, P=O), 1020 (s, P--O--C); MS (CI) m/e 345 (100, M+1), 344 (29.5, M+); Anal. calcd. for C12H21N6O4P.1/4H2O: C, 41.32; H. 6.21; N, 24.09. Found: C, 41.36; H. 6.02; N, 23.72.

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